C9

C9. Division may be regulated by internal and external factors.

 

Student Outcome: C9.1

Know that the cell produces gene products that regulate the cell cycle.

 

Go here to see the PowerPoint on how to draw a summary of the Cell cycle. 

 

Checkpoints in the cell cycle:

 

 

• There is an independent cell cycle control system made up of proteins that are different from the effector proteins that directly perform mitosis, G1, DNA replication, or G2. Brakes that can stop the cycle at specific checkpoints (a.k.a restriction points) regulate the control system. At checkpoints, feedback signals conveying information about the effector processes, or extracellular signals, can delay progress of the control system itself, so as to prevent it from triggering the next effector process before the previous one is finished. The two major checkpoints occur at G1, just before entry into S phase, and at G2 shortly before mitosis. There is an additional checkpoint before the exit from mitosis that corresponds to the point of no return at metaphase, of which we talked above. In yeast this checkpoint is call Start. This is also the point where cells enter G0 if the conditions are appropriate.

 

• The G2 checkpoint senses unreplicated DNA, which generates a signal that leads to cell cycle arrest, unless DNA replication is complete. Progression through the cycle is also stopped at the G2 checkpoint in response to DNA damage, such as that resulting from irradiation. This allows time for DNA repair before the M phase. The molecular mechanisms by which unreplicated or damaged DNA signals arrest at this checkpoint are still unknown.

 

• DNA damage arrests the cycle at G1 too, which allows time for repair before going into the S phase. At G1, damaged DNA induces the rapid synthesis of the p53 protein, which then signals cell cycle arrest. Mutations in the p53 gene are the most common genetic alterations in human cancers, illustrating the critical importance of cell cycle regulation in the life of multicellular organisms.

 

• The checkpoint at metaphase monitors the alignment of chromosomes on the mitotic spindle, thus ensuring that a complete set of chromosomes is distributed accurately to the daughter cells.

 

Here is a simple video summarising the cell cycle

 

Here is an animation which shows (simply) what happens at each stage of the cycle. Go there if the words don't make too much sense.

 

Source: http://darwin.nmsu.edu/~molbio/mcb520/lecture12.html

 

A visual summary - sorry, reasonably complex but skim it - and poorly numbered! Oh well!

 

 

Control of cell division

 

• There exist a variety of mechanisms that allow an individual cell to control its own division

 

• These mechanisms can be both positive and negative, i.e., there exist some signals that must be present and other signals that must be absent for cell division to proceed

 

• Typically the cell cycle gets stuck in G1 phase if signals for cell division to proceed are not present

 

• Once the cell cycle proceeds to S phase, the cell is committed to reproducing (i.e., are committed to proceeding through M phase and cytokinesis)

 

• Genes associated with various mechanisms of restraint of cell growth are called oncogenes (etc.) if they have been mutated to a lack of cell-growth-restrain

 

• Mechanisms of restraint include

 

• Lack of ability to divide indefinitely (are not immortal)

 

• Lack of ability to divide when in contact on all sides by other cells

 

• Lack of ability to divide in the absence of extracellular growth factors

 

Source: http://www.mansfield.ohio-state.edu/~sabedon/campbl12.htm

 

This animation, though dry, shows how a hormone (thyroxine) can  affect the production of proteins.

 

Can't recommend this video as it is very complex - but there isn't much out there that covers the cell cycle.

 

This is a bit better - a little corny and the accents may put you off, plus it takes a while to load - but try it.

This is a game you can play developed by the Nobel Prize people.

Finally, here is a really simple presentation on the cell cycle.

 

This is an amazing story - they are called HeLa cells - described as some of the most important cells every studied. Read about the story in Wikipedia.

The following video is a sample of HeLa cells dividing over a 27 hour period. It is no wonder that the person that these came from (Henrietta Lacks) died 8 months after being diagnosed with this extremely aggressive cancer.

 

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Student Outcome: C9.2

Understand that hormones may regulate cell division.

 

Normally, hormones from different places in the body interact with receptors on the cell surface and stimulate cell division. The genes inside cells contain instructions for making these hormone receptors. Sometimes the substitution of a single base in a gene is enough to alter the receptors and prevent the cell from responding to hormone signals.

 

Source: http://www.wv-hsta.org/TeacherInfo/NIH_Modules/uv/matter_proc10.htm

 

Cell signalling (Source: http://www.learner.org/courses/biology/units/cancer/images.html)
A signal (in this example, a growth factor) binds to a tyrosine kinase receptor on the outside of the cell. This activates the membrane protein (through the addition of phosphate groups), which in turn activates proteins in the cytoplasm such as kinases. Several other proteins may be involved in the cascade, ultimately activating one or more transcription factors. The activated transcription factors enter the nucleus, where they stimulate the expression of the genes that are under the control of that factor. This is an example of the RAS pathway, which results in cell division.

 

Short video showing how hormones are involved in cell division - don't blink though!

 

Go here to see how adrenaline can influence gene regulation.

 

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Student Outcome: C9.3

Understand that carcinogens upset the normal controls of cell division by causing mutations.

 

Animals are multicellular organisms that require the normal function of all the organs of the body. These organs are developed from different tissues and each of the tissues are products of cell division. For the body to function normally, the organs and tissues must communicate to control the development of the cells and tissues. Otherwise, uncontrolled cell growth in one part of the body could infringe on the development of other cells or tissues. Then the normal functions of the individual would be seriously impaired. Research over many years has shown that these control networks have a strong genetic component. This research has recently benefited from the study of the oncogenes of retroviruses and related protooncogenes that are found in animals.

 

Oncogenes have been shown many times to be associated with cancer and uncontrolled cellular growth. This growth can lead to tumors. Two types of tumors exist. Malignant tumors can induce secondary tumors by the release of cells that can lodge and begin growing in another location of the body. Benign tumors are cells that remain in the initial location.

 

Source: http://www.ndsu.nodak.edu/instruct/mcclean/plsc431/cellcycle/cellcycl2.htm

 

This is a summary of what has to happen when before a cell becomes cancerous

 

Here are some breast cancer cells dividing over a two day period.

 

Good source of information: http://www.insidecancer.org/

 

Good introduction here by NOVA on cancer - includes three animations. The first one is the most relevant.

 

Here is an animation by Dolan DNA about a cell responding to external signals.

 

As an aside - what happens when cells go rogue?  Bring on the peforins!